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Prof. Dr. Nils-Göran Larsson

Principal Investigator, Director of the MPI for Biology of Ageing

Prof. Dr. Nils-Göran Larsson
Principal Investigator, Director of the MPI for Biology of Ageing
Tel.  +49 221 4726 0
info[at]age.mpg.de

Max-Planck-Institut für Biologie des Alterns
Gleueler Str. 50 A
50931 Köln
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Nils-Göran Larsson

The team supporting Prof. Dr. Nils-Göran Larsson performs research on the mitochondrial genome and also examines the influence of mutations of mitochondrial genes on the aging process. The scientists were able to prove that the combination of mutations, passed on by the mother, and de novo mutations may trigger or amplify illnesses. Furthermore the scientists were able to identify specific mechanisms that prevent the inheritance of DNA mutations in the mitochondria. Currently Prof. Dr. Larsson is cooperating with the Lead Discovery Center, daughter of Max Planck Innovation, GmbH, to develop molecules through which the gene expression and thus the performance of the mitochondria can be regulated. This would provide the possibility to influence cell aging or mitochondrial diseases to name two examples.

Our research: The team led by Prof. Dr. Nils-Göran Larsson focuses on examining the mitochondrial genome. Mutations in the mitochondrial DNA may trigger premature aging processes.
Prof. Larsson and his team of scientists study the molecular mechanisms through which the mitochondrial genome is passed on. They concentrate on a deeper molecular understanding of the mitochondrial gene expression. The scientists examine the way mitochondrial DNA is transcribed and translated and how mutations influence the aging-process or become the elicitor of aging-associated diseases. The team cooperates with partners in the Lead Discovery Center, daughter of Max Planck Innovation GmbH, in Dortmund on a translational project for the development of so-called “small molecules” which influence the mitochondrial transcription and thus the gene expression.

Our successes: Together with his team Prof. Larsson succeeded in showing that mutations of the mitochondrial DNA induce cell aging. Such mutations are only transmitted by the mother. In combination with newly occurring mutations they can create synergies that may provoke and amplify disease and aging.
Unlike the inheritance of nuclear DNA, no recombination of the genetic material takes place. Due to this, defects in the mitochondrial DNA can easily accumulate over generations. The scientists supporting Prof. Larsson were able to identify multiple mechanisms, which prevent the inheritance of DNA damage. By decoding these quality-control-mechanisms, Prof. Larsson’s team made a fundamental contribution to the mitochondrial genome research and its role in the aging-process.

Our goals: The team cooperates with partners in the Lead Discovery Center in Dortmund on a translational project for the development of so-called „small molecules“. With the aid of these molecules mitochondrial transcription might prospectively be enhanced or constrained and thus influence the gene expression. These molecular tools will henceforth allow the regulation of the mitochondrial functions.

Our methods/techniques: In order to comprehend the structure of the mitochondria and their DNA, the researchers utilized different state-of-the-art techniques, among these high-resolution microscopy of mitochondria and protein structure determination by crystallography. By the means of super-resolution-microscopy, electron microscopy and electron cryotomography Prof. Larsson also examines packaging of the mitochondrial DNA into nucleoids, which holds the genetic material of mitochondria.

Figures
Figure 1
Figure 2
Figure 3
 

Figure 1: Schematic drawing of the life cycle of mitochondrial DNA (mtDNA) during the development
of oocytes in mice.

Figure 2: Schematic drawing of a mitochondrium, mitochondrial DNA and the complexes of protein synthesis. The right window shows a zoom into a part of mitochondrial DNA (blue) that is covered U-shape-like with the TFAM protein (yellow), the main component of the nucleoid.

Figure 3: Mitochondrial network in a mouse fibroblast visualized by Mitotracker staining.

EXTERNAL Cooperations
  • Prof. Dr. M. Falkenberg Gustafsson, University of Gothenburg, SE
  • Prof. Dr. A. Filipovska, University of Western Australia, Perth, AU
  • Prof. Dr. C. Gustafsson, University of Gothenburg, SE
  • Prof. Dr. S. Jakobs, Max Planck Institute for Biophysical Chemistry, Göttingen, DE
  • Prof. Dr. W. Kühlbrandt, Max Planck Institute for Biophysics, Frankfurt, DE
  • Prof. Dr. O. Rackham, University of Western Australia, Perth, AU